Alcohol has a biphasic effect on the body, which is to say that its effects change over time. [1] Initially, alcohol generally produces feelings of relaxation and cheerfulness, but further consumption can lead to blurred vision and coordination problems. Cell membranes are highly permeable to alcohol, so once alcohol is in the bloodstream it can diffuse into nearly every biological tissue of the body. After excessive drinking, unconsciousness can occur and extreme levels of consumption can lead to alcohol poisoning and death (a concentration in the blood stream of 0.55% will kill half of those affected). Death can also occur through asphyxiation by vomit. An appropriate first aid response to an unconscious, drunken person is to place them in the recovery position.

Intoxication frequently leads to a lowering of one's inhibitions, and intoxicated people will sometimes do things they would not do while sober, often overlooking social, moral, and legal considerations. Conversely, some studies have suggested that intoxicated people have much greater control over their behavior than is generally recognized. [1]

Some people's DNA code calls for a different acetaldehyde dehydrogenase, resulting in a more potent alcohol dehydrogenase. This leads to a buildup of acetaldehyde after alcohol consumption, causing the alcohol flush reaction with hangover-like symptoms such as flushing, nausea, and dizziness. These people are unable to drink much alcohol before feeling sick, and are therefore less susceptible to alcoholism.[2][3] This adverse reaction can be artificially reproduced by drugs such as disulfiram, which are used to treat chronic alcoholism by inducing an acute sensitivity to alcohol.

Dehydration

Overconsumption can therefore lead to dehydration (the loss of water).

Hangovers

A common after-effect of ethanol intoxication is the unpleasant sensation known as hangover, which is partly due to the dehydrating effect of ethanol. Hangover symptoms include dry mouth, headache, nausea, and sensitivity to light and noise. These symptoms are partly due to the toxic acetaldehyde produced from alcohol by alcohol dehydrogenase, and partly due to general dehydration. The dehydration portion of the hangover effect can be mitigated by drinking plenty of water between and after alcoholic drinks. Other components of the hangover are thought to come from the various other chemicals in an alcoholic drink, such as the tannins in red wine, and the results of various metabolic processes of alcohol in the body, but few scientific studies have attempted to verify this. Consuming water between drinks and before bed is the best way to prevent or lessen the effects of a hangover.

Beneficial effects of alcohol

The World Health Organization (WHO) reports that there is convincing evidence that "low to moderate alcohol intake" results in a decreased risk of coronary heart disease.[4] However, the WHO cautions that "other cardiovascular and health risks associated with alcohol do not favour a general recommendation for its use."[5]

However, a study of red wine published in the American Journal of Clinical Nutrition, found that alcohol-free red wine had the same health benefits as the alcoholic wine, and that the alcohol may actually shorten the benefits.[9]Flavonoids believed to be protective against coronary heart disease and some types of cancer, are present in wine due to its fermentation from grapes. These left the blood more quickly when alcohol was consumed.[9]

Moderate drinkers tend to have better health and live longer than those who abstain from alcohol or are heavy drinkers[citation needed], but this average difference may possibly be explained in part by the fact that a fraction of abstainers from alcohol are ex-alcoholics or those who have health problems or take drugs that preclude the use of alcohol. See Alcohol consumption and health.

Effects by doses

Different concentrations of alcohol in the human body have different effects on the subject. The following lists the effects of alcohol on the body, depending on the blood alcohol concentration or BAC.[10][11][12] Also, tolerance varies considerably between individuals.

Please note: the BAC percentages provided below are just estimates and used for illustrative purposes only. They are not meant to be an exhaustive reference; please refer to a healthcare professional if more information is needed.

Moderate doses

Although alcohol is typically thought of purely as a depressant, at low concentrations it can actually stimulate certain areas of the brain. Alcohol sensitises the N-methyl-D-aspartate (NMDA) system of the brain, making it more receptive to the neurotransmitter glutamate. Stimulated areas include the cortex, hippocampus and nucleus accumbens, which are responsible for thinking and pleasure seeking. Another one of alcohol's agreeable effects is body relaxation, possibly caused by heightened alpha brain waves surging across the brain. Alpha waves are observed (with the aid of EEGs) when the body is relaxed. Heightened pulses are thought to correspond to higher levels of enjoyment.

A well-known side effect of alcohol is lowering inhibitions. Areas of the brain responsible for planning and motor learning are dulled. A related effect, caused by even low levels of alcohol, is the tendency for people to become more animated in speech and movement. This is due to increased metabolism in areas of the brain associated with movement, such as the nigrostriatal pathway. This causes reward systems in the brain to become more active, and combined with reduced understanding of the consequences of their behavior, can induce people to behave in an uncharacteristically loud and cheerful manner.

Behavioral changes associated with drunkenness are, to some degree, contextual. A scientific study found that people drinking in a social setting significantly and dramatically altered their behavior immediately after the first sip of alcohol, well before the chemical itself could have filtered through to the nervous system. Likewise, people consuming non-alcoholic drinks often exhibit drunk-like behavior on a par with their alcohol-drinking companions even though their own drinks contained no alcohol whatsoever. [citation needed]

Excessive doses

The effect alcohol has on the NMDA receptors, earlier responsible for pleasurable stimulation, turns from a blessing to a curse if too much alcohol is consumed. NMDA receptors start to become unresponsive, slowing thought in the areas of the brain they are responsible for. Contributing to this effect is the activity which alcohol induces in the gamma-aminobutyric acid system (GABA). The GABA system is known to inhibit activity in the brain. GABA could also be responsible for the memory impairment that many people experience. It has been asserted that GABA signals interfere with the registration and consolidation stages of memory formation. As the GABA system is found in the hippocampus, (among other areas in the CNS), which is thought to play a large role in memory formation, this is thought to be possible.

Blurred vision is another common symptom of drunkenness. Alcohol seems to suppress the metabolism of glucose in the brain. The occipital lobe, the part of the brain responsible for receiving visual inputs, has been found to become especially impaired, consuming 29% less glucose than it should. With less glucose metabolism, it is thought that the cells aren't able to process images properly.

Often, after much alcohol has been consumed, it is possible to experience vertigo, the sense that the room is spinning (sometimes referred to as 'The Spins'). This is associated with abnormal eye movements called nystagmus, specifically positional alcohol nystagmus. In this case, alcohol has affected the organs responsible for balance (vestibular system), present in the ears. Balance in the body is monitored principally by two systems: the semicircular canals, and the utricle and saccule pair. Inside both of these is a flexible blob called a cupula, which moves when the body moves. This brushes against hair cells in the ear, creating nerve impulses that travel through the vestibulocochlear nerve (Cranial nerve VIII) in to the brain. However, when alcohol gets in to the bloodstream it distorts the shape of the cupola, causing it to keep pressing on to the hairs. The abnormal nerve impulses tell the brain that the body is rotating, causing disorientation and making the eyes spin round to compensate. When this wears off (usually taking until the following morning) the brain has adjusted to the spinning, and interprets not spinning as spinning in the opposite direction causing further disorientation. This is often a common symptom of the hangover.[citation needed]

Anterograde amnesia, colloquially referred to as "blacking out", is another symptom of heavy drinking.

Another classic finding of alcohol intoxication is ataxia, in its appendicular, gait, and truncal forms. Appendicular ataxia results in jerky, uncoordinated movements of the limbs, as though each muscle were working independently from the others. Truncal ataxia results in postural instability; gait instability is manifested as a disorderly, wide-based gait with inconsistent foot positioning. Ataxia is responsible for the observation that drunk people are clumsy, sway back and forth, and often fall down. It is probably due to alcohol's effect on the cerebellum.

Chronic alcohol ingestion over many years can produce atrophy of the vermis, which is the part of the cerebellum responsible for coordinating gait; vermian atrophy produces the classic gait findings of alcohol intoxication even when its victim is not inebriated.

Severe drunkenness and hypoglycemia can be mistaken for each other on casual inspection, with potentially serious medical consequences for diabetics. Measurement of the serum glucose and ethanol concentrations in comatose individuals is routinely performed in the emergency department or by properly-equipped prehospital providers and easily distinguishes the two conditions.

Pharmacology

At low or moderate doses, alcohol primarily acts as an unselective GABAAagonist. Alcohol binds to several different subtypes of GABAA, but not to others. The main subtypes responsible for the subjective effects of alcohol are the α1β3γ2, α5β3γ2, α4β3δ and α6β3δ subtypes, although other subtypes such as α2β3γ2 and α3β3γ2 are also affected. Activation of these receptors causes most of the effects of alcohol such as relaxation and relief from anxiety, sedation, ataxia and increase in appetite and lowering of inhibitions which can cause a tendency towards violence in some people.[13][14][15][16][17][18][19]

At higher dose ranges, other targets also become important. Alcohol at high doses acts as an antagonist of the NMDA receptor, and since the NMDA receptor is involved in learning and memory, this action is thought to be responsible for the "memory blanks" that can occur at extremely high doses of alcohol. People with a family history of alcoholism may exhibit genetic differences in the response of their NMDA glutamate receptors as well as the ratios of GABA-A subtypes in their brain. Alteration of NMDA receptor numbers in chronic alcoholics is likely to be responsible for some of the symptoms seen in delerium tremens during severe alcohol withdrawal, such as delerium and hallucinations. Other targets such as sodium channels can also be affected by high doses of alcohol, and alteration in the numbers of these channels in chronic alcoholics is likely to be responsible for the convulsions that can occur in acute alcohol withdrawal, as well as other effects such as cardiacarrhythmia. Also chronic NMDA receptor blockade may produce apoptosis in neurons which is likely to one of the factors involved in producing the brain damage seen in long-term alcoholic patients. Other targets that are affected by alcohol include cannabinoid, opioid and dopamine receptors, although it is unclear whether alcohol affects these directly or if they are affected by downstream consequences of the GABA/NMDA effects.[20][21][22][23][24][25][26][27]

Animal and Insect Models

There have been some attempts to use animal and insect models to study the effects of ethanol on humans. Other creatures are not immune to the effects of alcohol:

Many of us have noticed that bees or yellow jackets cannot fly well after having drunk the juice of overripe fruits or berries; bears have been seen to stagger and fall down after eating fermented honey; and birds often crash or fly haphazardly while intoxicated on ethanol that occurs naturally as free-floating microorganisms convert vegetable carbohydrates to alcohol.[28]

Birds may have even been killed by excessive consumption of alcohol.[29]

In Sweden, drunken moose have been observed. The theory is that they had eaten large amounts of overly ripe berries.

As a result, animal and insect models are fairly attractive. Heberlein et al. conducted studies of fruit fly intoxication at the University of California, San Francisco in 2004.[30]
The brains and nervous systems of bees bear similarities to those of humans, so honey bees are used in studies of the effect of alcohol.[31][32][33] The value of antabuse (disulfiram) as a treatment for alcoholism has been tested using a bee model.[34]

Ulrike Heberlein's group at University of California, San Francisco has used fruit flies as models of human inebriation and even identified genes that seem to be responsible for alcohol tolerance accumulation (believed to be associated with veisalgia, or hangover), and produced genetically engineered strains that do not develop alcohol tolerance[35][36][37][38]